Mortality in sporadic primary hyperparathyroidism: nationwide cohort study of multiple parathyroid gland disease

BACKGROUND: The risk of dying from primary hyperparathyroidism (pHPT) is controversial and has been explored mainly in single parathyroid gland disease. The present study investigates mortality in pHPT due to multiple parathyroid gland disease. METHODS: We used the nationwide Swedish In-patient Register and Cause-of-Death Registry to compare the mortality in 3485 Swedish patients subjected to parathyroidectomy during 1964 to 1999 with that of the Swedish population (standardized for age, gender, and calendar year). The patient cohort includes 36,596 person years. RESULTS: Increased risk of death beyond the first postoperative year (standardized mortality ratio, 1.4; 95% CI, 1.37-1.52) was found in both sexes and for all age intervals below 80 years. The increased risk persisted more than 15 years postoperatively and related to cardiovascular diseases, diabetes mellitus, urogenital diseases, and malignant disorders. The increased risk of dying in cardiovascular diseases normalized during 1990 to 1999. CONCLUSIONS: pHPT caused by multiple parathyroid gland enlargement is associated with an excessive mortality similar to pHPT of single parathyroid adenoma. The findings substantiate that modern modes of surgical treatment for pHPT normalize the risk of dying from cardiovascular complications and that the hyperpararthyroid state per se is the possible cause of the premature death.     

Position of anterior capsulorhexis and posterior capsule opacification

PURPOSE: To evaluate whether the position of the anterior continuous curvilinear capsulorhexis influences the rate of posterior capsule opacification (PCO). METHODS: A total of 119 patients, aged 61-86 years, underwent cataract surgery with phacoemulsification performed by a single surgeon. The patients were randomized to implantation with either a silicone intraocular lens (IOL) (SI40NB, Allergan) or an AcrySof IOL (MA60BM, Alcon). Three years after surgery, the rate of PCO was analysed using the evaluation of posterior capsule opacification computer software (EPCO). The results were related to the capsulorhexis position, which was assessed with a retroillumination photograph. RESULTS: If the capsulorhexis was located partially or completely off the optics of the IOL, compared to totally on the IOL, significantly more PCO was found (p = 0.0014). When comparing within each IOL type, patients with AcrySof IOLs were found to have significantly less PCO when the capsulorhexis was totally on the optic (p = 0.0048). This difference was also significant in the silicone group (p = 0.041). CONCLUSION: A relatively small and central capsulorhexis allowing for the complete covering of the IOL optics by the rhexis edges seems to protect against PCO in cataract surgery, with both round-edged silicone IOLs and sharp-edged hydrophobic acrylic IOLs.     

Neuronal expression of caspase-1 immunoreactivity in the rat central nervous system

Caspase-1/interleukin-1beta (IL-1beta)-converting enzyme (ICE) cleaves IL-1beta and IL-18 precursor proteins to the active forms of these proinflammatory cytokines. Since both cytokines are constitutively expressed in the brain, we investigated whether this is also the case for caspase-1. Using an antibody raised against the p10-subunit of the active enzyme, constitutive expression of caspase-1 immunoreactivity was found in nerve cells in the arcuate nucleus and in nerve fibres throughout the brain. Co-localisation with alpha-melanocyte stimulating hormone was demonstrated. The distribution pattern of caspase-1 immunoreactive structures is consistent with a role to produce mature IL-1beta in regions where IL-1beta mediates fever and sleep.     

Traumatic experiences and dissociative symptoms among Swedish adolescents. A pilot study using Dis-Q-Sweden

The aim of this study was to explore the occurrence of dissociative symptoms in relation to reported traumatic experiences among adolescents. A normative sample of 216 adolescents and a clinical sample of 30 cases with a history of traumatization were given the Swedish translation of Dissociation Questionnaire, DIS-Q. The results showed that 8.8% of the adolescents reported scores above the cut-off score of 2.5 on the Dis-Q-Sweden, with a female-male ratio of 2.6:1. In the normative sample, 53 (24.5%) of the adolescents reported one or more trauma experiences. The adolescents who self-reported trauma experiences in the normative sample scored higher on the total Dis-Q-Sweden scores and on three of the four subscales compared to the adolescents with no such experiences. The clinical group exhibited significantly higher Dis-Q-Sweden scores than the normative sample on every scale, with 60% above the cut-off score. The study confirms the results from earlier studies that adolescents with a history of trauma exhibit more dissociative symptoms in this study according to Dis-Q-Sweden. The impact of trauma qualities and background factors on the development of dissociative symptoms need to be studied further.     

Use and interpretation of on/off diaries in Parkinson's disease

OBJECTIVE: To explore the use and interpretation of self reported on/off diary data for assessment of daily motor fluctuations in Parkinson's disease. METHODS: 26 consecutive non-demented patients with fluctuating Parkinson's disease received standardised training on how to fill out the four category CAPSIT-PD on/off diary, followed by four hours of clinical observation and four weeks of daytime on/off diaries every 30 minutes at home. RESULTS: Overall patient-clinician agreement in diary entries was good (kappa = 0.62; weighted kappa = 0.84). Agreement for individual diary categories was good for "off" and "on with dyskinesias" (kappa = > or =0.72), but moderate for "partial off" and "on" (kappa = 0.49). The overall validity of patient kept diaries was supported by expected symptom severity variability across diary categories, as assessed in the clinic. One day's home diary data failed to predict outcomes from the full four weeks for all diary categories, and data from three days failed to yield good prediction (predefined as R(2) = > or =approximately 0.7) for the time spent in "off" and "partial off". Data from one week yielded good prediction (R(2) = > or =0.74) in all instances except "partial off", which could not be well predicted even when two weeks' home diary data were considered (R(2) = 0.52). CONCLUSIONS: The data provide support for the overall accuracy and validity of the four category CAPSIT-PD on/off diary, but suggest that a three category diary format may improve accuracy and validity. Interpretation of diary data beyond the assessed time frame should be made with caution unless diaries have been kept for sufficiently long periods.     

Comparison of different routes of vaccination for eliciting antibody responses in the human stomach

Determination of optimal routes to induce mucosal immune responses locally in the stomach and duodenum are important steps in the development of vaccines against Helicobacter pylori infection. In this study, we immunized H. pylori-infected individuals either nasally or rectally with a model antigen, i.e. cholera toxin B subunit, and compared the immune responses after these routes with the responses after oral or intrajejunal vaccination. Specific antibody levels in serum as well as specific antibody levels and antibody-secreting cells in biopsies from antrum and duodenum were determined by ELISA and ELISPOT methods. In contrast to oral vaccination, nasal and rectal vaccination did not induce significant increases in specific antibody-secreting cells either in the antrum or duodenum. Furthermore, when analyzing the antibody levels in saponin extracted biopsies, intrajejunal vaccination was superior to both nasal and rectal vaccination in inducing antigen-specific IgA levels in the stomach. We conclude that oral vaccination is the optimal route for induction of antigen-specific IgA antibody responses in the stomach and duodenum of humans, while nasal or rectal vaccination is less suitable for this purpose.     

The Swedish Family-Cancer Database: Update,Application to Colorectal Cancer and Clinical Relevance

The Swedish Family-Cancer Database has been used for almost 10 years in the study of familial risks at all common sites. In the present paper we describe some main features of version VI of this Database, assembled in 2004. This update included all Swedes born in 1932 and later (offspring) with their biological parents, a total of 10.5 million individuals. Cancer cases were retrieved from the Swedish Cancer Registry from 1958-2002, including over 1.2 million first and multiple primary cancers and in situ tumours. Compared to previous versions, only 6.0% of deceased offspring with a cancer diagnosis lack any parental information. We show one application of the Database in the study of familial risks in colorectal adenocarcinoma, with defined age-group and anatomic site specific analyses. Familial standardized incidence ratios (SIRs) were determined for offspring when parents or sibling were diagnosed with colon or rectal cancer. As a novel finding it was shown that risks for siblings were higher than those for offspring of affected parents. The excess risk was limited to colon cancer and particularly to right-sided colon cancer. The SIRs for colon cancer in age matched populations were 2.58 when parents were probands and 3.81 when siblings were probands; for right-sided colon cancer the SIRs were 3.66 and 7.53, respectively. Thus the familial excess (SIR-1.00) was more than two fold higher for right-sided colon cancer. Colon and rectal cancers appeared to be distinguished between high-penetrant and recessive conditions that only affect the colon, whereas low-penetrant familial effects are shared by the two sites. Epidemiological studies can be used to generate clinical estimates for familial risk, conditioned on numbers of affected family members and their ages of onset. Useful risk estimates have been developed for familial breast and prostate cancers. Reliable risk estimates for other cancers should also be seriously considered for routine clinical recommendations, because practically all cancers show a familial effect and the risks are high for some of the rare neoplasms. The implementation of a unified management plan for familial cancers at large will be a major challenge to the clinical genetic counselling community.     

Tamoxifen inhibits secretion of vascular endothelial growth factor in breast cancer in vivo

Vascular endothelial growth factor (VEGF) is considered a key mediator of tumor angiogenesis, including neovascularization in human breast cancer. High tissue VEGF levels appear to correlate with poor prognosis and decreased overall survival in node-positive and node-negative breast cancer patients. Hormonal regulation of VEGF expression has been demonstrated, and some reports indicate that tamoxifen, a partial estrogen receptor agonist, increases VEGF mRNA in breast cancer cells. These results appear to contradict the efficacy of tamoxifen as an adjuvant for estrogen-dependent breast cancer, yet clinical data show that tamoxifen prevents metastasis and increases overall survival. In this study, we confirmed previous studies showing that intracellular levels of VEGF in vitro increased in response to tamoxifen to levels similar to those observed after estrogen treatment. To further study hormonal effects on the release of VEGF, we used microdialysis to sample the extracellular space, where VEGF is biologically active, in solid tumors in situ. We show for the first time that tamoxifen decreased extracellular VEGF in vivo in solid MCF-7 tumors in nude mice. These in vivo findings were confirmed in vitro where extracellular VEGF in the cell culture medium was decreased significantly by tamoxifen treatment. Furthermore, we illustrate that microdialysis is a viable method that may be applied in human breast tissue to detect soluble VEGF in situ released by the tumor.     

Anterograde delivery of brain-derived neurotrophic factor to striatum via nigral transduction of recombinant adeno-associated virus increases neuronal death but promotes neurogenic response following stroke

To explore the role of brain-derived neurotrophic factor for survival and generation of striatal neurons after stroke, recombinant adeno-associated viral vectors carrying brain-derived neurotrophic factor or green fluorescent protein genes were injected into right rat substantia nigra 4-5 weeks prior to 30 min ipsilateral of middle cerebral artery occlusion. The brain-derived neurotrophic factor-recombinant adeno-associated viral transduction markedly increased the production of brain-derived neurotrophic factor protein by nigral cells. Brain-derived neurotrophic factor was transported anterogradely to the striatum and released in biologically active form, as revealed by the hypertrophic response of striatal neuropeptide Y-positive interneurons. Animals transduced with brain-derived neurotrophic factor-recombinant adeno-associated virus also exhibited abnormalities in body posture and movements, including tilted body to the right, choreiform movements of left forelimb and head, and spontaneous, so-called 'barrel' rotation along their long axis. The continuous delivery of brain-derived neurotrophic factor had no effect on the survival of striatal projection neurons after stroke, but exaggerated the loss of cholinergic, and parvalbumin- and neuropeptide Y-positive, gamma-aminobutyric acid-ergic interneurons. The high brain-derived neurotrophic factor levels in the animals subjected to stroke also gave rise to an increased number of striatal cells expressing doublecortin, a marker for migrating neuroblasts, and cells double-labelled with the mitotic marker, 5-bromo-2'-deoxyuridine-5'monophosphate, and early neuronal (Hu) or striatal neuronal (Meis2) markers. Our findings indicate that long-term anterograde delivery of high levels of brain-derived neurotrophic factor increases the vulnerability of striatal interneurons to stroke-induced damage. Concomitantly, brain-derived neurotrophic factor potentiates the stroke-induced neurogenic response, at least at early stages.